We propose to study the genetic control of immune responsiveness in mice to a series of synthetic polypeptide antigens. The genes controlling immune responsiveness are localized within the major histocompatibility complex, H-2. We have previously demonstrated that two genetically distinct genes control the response to the random linear terpolymer of L-amino acids-poly(glu53lys36phe11), termed GLphi. Both of these immune response (Ir) genes have been mapped in the I region of the H-2 complex. In this system, we propose to investigate the role of each gene in immune responsiveness and determine at what cell level the genes are expressed. In addition, we propose to investigate the genetic control of specific immune suppression, again using synthetic polypeptide antigens. We have previously demonstrated that this regulatory immune phenomenon is under H-2 linked genetic control by specific immune suppression genes, termed Is genes. We propose to map the Is genes within the H-2 complex, analyze if more than one gene is required for immune suppression, and determine the cells in which the Is genes are expressed.